Transcript 26-BrainNT2015.ppt

Brain Neurotransmitters
 Chemical substances released
by electrical impulses into the
synaptic cleft from synaptic
vesicles of presynaptic
membrane
 Diffuses to the postsynaptic
membrane
 Binds to and activates the
receptors
 Leading to initiation of new
electrical signals or inhibition
of the post-synaptic neuron
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Adrenaline / NE
Ach
Glutamate
GABA
Serotonin
Dopamine
Classes of Receptors
 Metabotropic = trans membrane receptor acts
through a secondary messenger
 Ionotropic = Ligand gated ion channel
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Norepinephrine System
The Locus Coeruleus/Norepinephrine
System
• Very wide-spread projection system
• LC is activated by stress and co-ordinates
responses via projections to thalamus,
cortex, hippocampus, amygdala,
hypothalamus, autonomic brainstem centers,
and the spinal cord
• Sleep
• Attention/Vigilance
Locus coeruleus neurons fire as a function of vigilance
and arousal
Irregular firing during quiet wakefulness
Sustained activation during stress
Their firing decreases markedly during slow-wave
sleep
and virtually disappears during REM sleep.
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Norepinephrine (NE) Implicated in StressRelated Disorders
• Depression
• Withdrawal from some drugs of abuse
• Other stress-related disorders such as
panic disorder.
PGi: Nucleus paragigantocellularis
PrH: Perirhinal Cortex
 Major neurotransmitter in the peripheral
nervous system
 Produced by the neurons in the parietal lobes
of the brain
 Associated with
 Thought
 Memory
 Muscular coordination
 Speed of information processing in the brain
 Production of myelin sheath
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ACh influences mental processes such as
Learning
Memory
Sleeping
Dreaming.
Alzheimer’s Disease- the most common form of
dementia that is associated with acetylcholine
Damage to Ach producing cells in the basal
forebrain
Bipolar disorder
Mood swings
Depression
Glutamate
 It is the most commonly
found neurotransmitter in
the brain.
 It is always excitatory.
 Glutamate is formed (alpha
ketoregulation) Kreb’s cycle
 > > > carried into
astrocytes > > > converted
to glutamine > > > passed
on to glutaminergic
neurones
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 Important role in
 Learning and memory
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GABAergic neurons
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Gamma Aminobutyric acid (GABA)
 Inhibitory neurotransmitter of
CNS and is also found in retina.
 Formed by decarboxylation of
glutamate.
 Three types of GABA receptors
e.g. GABAA B & C.
 GABA A & B receptors are widely
distributed in CNS.
 GABAC are found in retina only
 GABA B are metabotropic (Gprotein) in function.
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 GABA is the main inhibitory neurotransmitter
in the central nervous system (CNS).
 GABAergic inhibition is seen at all levels of
the CNC
 (Hypothalamus, hippocampus, cerebral cortex
and cerebellar cortex.
 GABA interneurones are abundant in the
brain, with 50% of the inhibitory synapses in
the brain being GABA mediated.
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GABAergic neurons
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Serotonin
The serotonin pathways in
the brain:
The principal centers for
serotonergic neurons are the
rostral and caudal raphe
nuclei
>>>> axons ascend to the
cerebral cortex, limbic &
basal ganglia
Serotonergic nuclei in the
brain stem >>>> descending
axons (terminate in the
medulla& spinal cord
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Serotonin (5-HT) Disorders
• Depression
• Anxiety
Dopaminergic Pathways
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Dopaminergic Pathways
Dopamine is transmitted via
three major pathways:
1- The first extends from
the substantia nigra to the
caudate nucleus-putamen
(neostriatum) and is
concerned with sensory
stimuli and movement.
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 2- The second pathway
prject to the mesolimbic
forebrain
 Related to cognitive,
reward and emotional
behavior
 3- The third pathway,
known as the tuberoinfundibular system
 Rleated to neuronal
control of the
hypothalmic-pituatory
endocrine system.
Dopaminergic Pathways
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Dopaminergic Pathways/Functions
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Dopaminergic neurons disorders
Schezophrenia.
Parkinson’s Disease.
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Neurotransmitter
Postsynapti
c effect
Derived
from
Site of
synthesis
Postsynaptic
receptor
Fate
Functions
1.Acetyl choline
(Ach)
Excitatory
Acetyl coA +
Choline
Cholinergic
nerve endings
Cholinergic
pathways of
brainstem
1.Nicotinic
2.Muscarini
c
Broken by
acetyl
cholinesterase
Cognitive
functions e.g.
memory
Peripheral action
e.g.
cardiovascular
system
2. Catecholamines
i. Epinephrine
(adrenaline)
Excitatory
in some
but
inhibitory
in other
Tyrosine
produced in
liver from
phenylalanin
e
Adrenal
medulla and
some CNS
cells
Excites
both alpha
α &
beta β
receptors
ii.Norepinephrine
Excitatory
Tyrosine,
found in
pons.
Reticular
formation,
locus
coerules,
thalamus,
mid-brain
Begins inside
axoplasm of
adrenergic
nerve ending is
completed
inside the
secretary
vesicles
α1 α2
β1 β2
1.Catabolized
to inactive
product through
COMT & MAO
in liver
2.Reuptake into
adrenergic
nerve endings
3.Diffusion
away from
nerve endings to
body fluid
For details refer
ANS. e.g. fight
or flight,
on
heart, BP,
gastrointestinal
activity etc.
Norepinehrine
controls attention
& arousal,
sleep/wake cycle.
iii. Dopamine
Excitatory
Tyrosine
CNS,
concentrated
in basal ganglia
and dopamine
pathways e.g.
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nigrostriatal,
mesocorticolim
D1 to D5
receptor
Same as above
Sensory motor
Cognetive/emotion
al behavior
Endocrine
Hypothalamic
Decreased
Site of
synthesis
Neurotransmitt
er
Postsynaptic
effect
3. serotonin
(5HT)
Excitatory
Tryptophan
CNS, Gut
(chromaffin
cells)
Platelets &
retina
4. Histamine
Excitatory
Histidine
5. Glutamate
Excitatory
75% of
excitatory
transmissio
n in the
brain
By reductive
amination of
Kreb’s cycle
intermediate
α –
ketoglutarate.
Derived from
Postsynaptic
receptor
Fate
Functions
5-HT1 to
5-HT 7
5-HT 2 A
receptor
mediate
platelet
aggregation &
smooth muscle
contraction
Inactivated by
MAO to form 5hydroxyindoleace
tic acid(5-HIAA)
in pineal body it
is converted to
melatonin
Mood control,
sleep, pain
feeling,
temperature, BP,
& hormonal
activity
Hypothalamu
s
Three types
H1, H2 ,H3
receptors
found in
peripheral
tissues & the
brain
Enzyme diamine
oxidase
(histaminase)
cause breakdown
Arousal, pain
threshold, blood
pressure, blood
flow control, gut
secretion,
allergic reaction
(involved in
sensation of itch)
Brain &
spinal cord
e.g.
hippocampus
Ionotropic and
metabotropic
receptors.
Three types
of ionotropic
receptors e.g.
NMDA, AMPA
and kainate
receptors.
It is cleared
from the brain
ECF by Na +
dependent uptake
system in
neurons and
neuroglia.
Long term
potentiation
involved in
memory and
learning by
causing Ca++
influx.
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Neurotransmitt
er
6. Aspartate
7. Gama amino
butyric
acid(GABA)
8. Glycine
Postsynaptic
effect
Excitatory
Derived from
Site of
synthesis
Acidic amines
Spinal
cord
Spinal cord
CNS
GABA – A
increases the
Cl conductance,
GABA – B is
metabotropic
works with G
– protein
GABA
transaminase
catalyzes.
GABA – C
found
exclusively in
the retina.
Metabolized by
transamination to
succinate in the
citric acid cycle.
GABA – A causes
hyperpolarization
(inhibition)
Anxiolytic drugs
like
benzodiazepine
cause increase in
Cl- entry into the
cell & cause
soothing effects.
GABA – B cause
increase
conductance of K+
into the cell.
Spinal
cord
Glycine
receptor
makes
postsynaptic
membrane
more
permeable to
Cl- ion.
Deactivated in
the synapse by
simple process of
reabsorbtion by
active transport
back into the
presynaptic
membrane
Glycine is
inhibitory
transmitted found
in the ventral
spinal cord. It is
inhibitory
transmitter to
Renshaw cells.
Major
inhibitory
mediator
Decarboxylati
on of
glutamate by
glutamate
decarboxylas
e (GAD) by
GABAergic
neuron.
Inhibitory
Is simple
amino acid
having amino
group and a
carboxyl
group
attached to a
carbon atom
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Postsynaptic
receptor
Fate
Functions
Aspartate & Glycine form an
excitatory / inhibitory pair in the
ventral spinal cord